Bottom Line:
Arc, an effector immediate early gene, and zif268, a regulatory transcription factor, have been implicated in synaptic plasticity underlying learning and memory.The timing of hippocampal Arc and zif268 expression coincides with the critical period for protein synthesis-dependent memory consolidation following fear conditioning.These findings suggest that altered Arc and zif268 expression are related to neural plasticity during the formation of fear memory.

ABSTRACTMemory consolidation requires transcription and translation of new protein. Arc, an effector immediate early gene, and zif268, a regulatory transcription factor, have been implicated in synaptic plasticity underlying learning and memory. This study explored the temporal expression profiles of these proteins in the rat hippocampus following fear conditioning. We observed a time-dependent increase of Arc protein in the dorsal hippocampus 30-to-90-minute post training, returning to basal levels at 4 h. Zif268 protein levels, however, gradually increased at 30-minute post training before peaking in expression at 60 minute. The timing of hippocampal Arc and zif268 expression coincides with the critical period for protein synthesis-dependent memory consolidation following fear conditioning. However, the expression of Arc protein appears to be driven by context exploration, whereas, zif268 expression may be more specifically related to associative learning. These findings suggest that altered Arc and zif268 expression are related to neural plasticity during the formation of fear memory.

fig1: (a) Schematic depicting the fear conditioning procedure used. Rats were killed at varying time points following training and brain tissue was dissected for western blot analysis. (b) Frozen brain tissue was microdissected from the dorsal hippocampus. Shaded regions are representative of the size and location of tissue collected for western blots. CS: conditional stimulus, UCS: unconditional stimulus, DH: dorsal hippocampus.

Mentions:
Before any experimentation, rats were adapted to handling and transportation procedures for 3 min each on 6 consecutive days. Rats were trained in a single 15-min session of auditory-cued fear conditioning (Figure 1(a)). After an initial 6-min baseline period, the rats received four presentations of white noise (72 dB, 10 s) that coterminated with a footshock (1.3 mA, 1 s). These four presentations were separated by a 90-second intertrial interval. The rats remained in the chamber for an additional 4 min following the last footshock before being returned to their home cages. This training protocol has previously been shown to produce both contextual and auditory-cued fear memories [28, 29, 33]. Additional groups of animals were created to control separately for auditory and contextual experience and shock stimulation. One group experienced the same training protocol but with no shock stimuli delivered (WN-CXT), and another group received footshock immediately upon placement in the chamber and removed shortly afterward (SHK-only).

fig1: (a) Schematic depicting the fear conditioning procedure used. Rats were killed at varying time points following training and brain tissue was dissected for western blot analysis. (b) Frozen brain tissue was microdissected from the dorsal hippocampus. Shaded regions are representative of the size and location of tissue collected for western blots. CS: conditional stimulus, UCS: unconditional stimulus, DH: dorsal hippocampus.

Mentions:
Before any experimentation, rats were adapted to handling and transportation procedures for 3 min each on 6 consecutive days. Rats were trained in a single 15-min session of auditory-cued fear conditioning (Figure 1(a)). After an initial 6-min baseline period, the rats received four presentations of white noise (72 dB, 10 s) that coterminated with a footshock (1.3 mA, 1 s). These four presentations were separated by a 90-second intertrial interval. The rats remained in the chamber for an additional 4 min following the last footshock before being returned to their home cages. This training protocol has previously been shown to produce both contextual and auditory-cued fear memories [28, 29, 33]. Additional groups of animals were created to control separately for auditory and contextual experience and shock stimulation. One group experienced the same training protocol but with no shock stimuli delivered (WN-CXT), and another group received footshock immediately upon placement in the chamber and removed shortly afterward (SHK-only).

Bottom Line:
Arc, an effector immediate early gene, and zif268, a regulatory transcription factor, have been implicated in synaptic plasticity underlying learning and memory.The timing of hippocampal Arc and zif268 expression coincides with the critical period for protein synthesis-dependent memory consolidation following fear conditioning.These findings suggest that altered Arc and zif268 expression are related to neural plasticity during the formation of fear memory.

ABSTRACTMemory consolidation requires transcription and translation of new protein. Arc, an effector immediate early gene, and zif268, a regulatory transcription factor, have been implicated in synaptic plasticity underlying learning and memory. This study explored the temporal expression profiles of these proteins in the rat hippocampus following fear conditioning. We observed a time-dependent increase of Arc protein in the dorsal hippocampus 30-to-90-minute post training, returning to basal levels at 4 h. Zif268 protein levels, however, gradually increased at 30-minute post training before peaking in expression at 60 minute. The timing of hippocampal Arc and zif268 expression coincides with the critical period for protein synthesis-dependent memory consolidation following fear conditioning. However, the expression of Arc protein appears to be driven by context exploration, whereas, zif268 expression may be more specifically related to associative learning. These findings suggest that altered Arc and zif268 expression are related to neural plasticity during the formation of fear memory.